活性和静止性溃疡性结肠炎中下调的粘膜自噬、α激酶-1和IL-17信号通路

IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY
Clinical and Experimental Gastroenterology Pub Date : 2022-07-27 eCollection Date: 2022-01-01 DOI:10.2147/CEG.S368040
Luiza Moraes Holst, Jonas Halfvarson, Marie Carlson, Charlotte Hedin, Robert Kruse, Carl Mårten Lindqvist, Daniel Bergemalm, Sven Almér, Francesca Bresso, Maria Ling Lundström, Dirk Repsilber, Mauro D'Amato, Åsa Keita, Henrik Hjortswang, Johan Söderholm, Johanna Sundin, Hans Törnblom, Magnus Simrén, Hans Strid, Maria K Magnusson, Lena Öhman
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引用次数: 2

摘要

背景:需要改善活动性和静止性结肠炎性肠病(IBD)的粘膜免疫谱,以制定治疗和预防炎症发作的治疗方案。因此,本研究旨在提供一个全面的粘膜特征,重点是活动性溃疡性结肠炎(UC活动性)、缓解期UC (UC缓解期)和活动性结肠克罗恩病(CD活动性)患者的免疫宿主反应。方法:收集47名研究对象的结肠活检,使用NanoString宿主反应面板进行基因表达和途径分析,包括776个基因和56个免疫相关途径。结果:与健康受试者(n=10)相比,活动性IBD患者(n=27)大多数粘膜基因表达和信号通路评分升高。然而,与健康受试者相比,活跃的IBD和UC缓解(n=10)均表现出与自噬、α激酶-1和IL-17信号通路相关的基因表达和信号通路评分降低。此外,与健康受试者相比,UC缓解的特征是与体内平衡相关的几种信号通路得分下降,同时单核细胞迁移途径得分增加。结肠粘膜基因表达在CD活性组(n=7)和UC活性组(n=20)之间无明显差异。结论:本研究表明,UC中自噬、α激酶-1和IL-17信号通路持续下调,与疾病活动无关。此外,缓解期UC患者呈现出独特的粘膜环境,可能阻止患者达到和维持真正的体内平衡。这些发现可能有助于更好地理解结肠IBD的缓解和复发模式,并指导未来的治疗和预防耀斑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis.

Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis.

Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis.

Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis.

Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn's disease (CD active).

Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.

Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.

Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.

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来源期刊
Clinical and Experimental Gastroenterology
Clinical and Experimental Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
5.10
自引率
0.00%
发文量
26
审稿时长
16 weeks
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